The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy
Open accessAbstract
Purpose: Fibroblast activation protein (FAP) is a membrane-bound protease that has limited expression in normal adult tissues but is highly expressed in the tumor microenvironment of many solid cancers. FAP-2286 is a FAP-binding peptide coupled to a radionuclide chelator that is currently being investigated in patients as an imaging and therapeutic agent. The potency, selectivity, and efficacy of FAP-2286 were evaluated in preclinical studies. Methods: FAP expression analysis was performed by immunohistochemistry and autoradiography on primary human cancer specimens. FAP-2286 was assessed in biochemical and cellular assays and in in vivo imaging and efficacy studies, and was further evaluated against FAPI-46, a small molecule–based FAP-targeting agent. Results: Immunohistochemistry confirmed elevated levels of FAP expression in multiple tumor types including pancreatic, breast, and sarcoma, which correlated with FAP binding by FAP-2286 autoradiography. FAP-2286 and its metal complexes demonstrated high affinity to FAP recombinant protein and cell surface FAP expressed on fibroblasts. Biodistribution studies in mice showed rapid and persistent uptake of 68 Ga-FAP-2286, 111 In-FAP-2286, and 177 Lu-FAP-2286 in FAP-positive tumors, with renal clearance and minimal uptake in normal tissues. 177 Lu-FAP-2286 exhibited antitumor activity in FAP-expressing HEK293 tumors and sarcoma patient-derived xenografts, with no significant weight loss. In addition, FAP-2286 maintained longer tumor retention and suppression in comparison to FAPI-46. Conclusion: In preclinical models, radiolabeled FAP-2286 demonstrated high tumor uptake and retention, as well as potent efficacy in FAP-positive tumors. These results support clinical development of 68 Ga-FAP-2286 for imaging and 177 Lu-FAP-2286 for therapeutic use in a broad spectrum of FAP-positive tumors.
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Cites
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A framework for advancing our understanding of cancer-associated fibroblasts
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“In cancers of epithelial origin, FAP expression is mainly restricted to the CAFs in the tumor microenvironment, which possesses diverse functions, such as stromatogenesis, reciprocal signaling interactions with cancer cells, and crosstalk with tumor-infiltrating leucocytes (6,12).”
BackgroundPhase 3 Trial of 177 Lu-Dotatate for Midgut Neuroendocrine Tumors
Strosberg, J., El-Haddad, G., Wolin, E., Hendifar, A., Yao, J., Chasen, B., Mittra, E., Kunz, P. L., Kulke, M. H., Jacene, H., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1607427 · Cited by 3,308
Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer
Sartor, O., de Bono, J., Chi, K. N., Fizazi, K., Herrmann, K., Rahbar, K., Tagawa, S. T., Nordquist, L. T., Vaishampayan, N., El-Haddad, G., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107322 · Cited by 2,864
68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer
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Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein–α
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A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts
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Cited by
Radiopharmaceuticals and their applications in medicine
Zhang, S., Wang, X., Gao, X., Chen, X., Li, L., Li, G., Liu, C., Miao, Y., Wang, R., & Hu, K. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02041-6 · Cited by 284
Metadata
- Authors
- Zboralski, D., Hoehne, A., Bredenbeck, A., Schumann, A., Nguyen, M., Schneider, E., Ungewiss, J., Paschke, M., Haase, C., von Hacht, J. L., Kwan, T., Lin, K. K., Lenore, J., Harding, T. C., Xiao, J., Simmons, A. D., Mohan, A.-M., Beindorff, N., Reineke, U., Smerling, C., & Osterkamp, F.
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 2022-05-24
- Volume
- 49
- Issue
- 11
- Pages
- 3651-3667
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- OpenAlex
- W4281400179
- Cited by
- 283
- References
- 47
- FWCI
- 18.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zboralski, D., Hoehne, A., Bredenbeck, A., Schumann, A., Nguyen, M., Schneider, E., Ungewiss, J., Paschke, M., Haase, C., von Hacht, J. L., Kwan, T., Lin, K. K., Lenore, J., Harding, T. C., Xiao, J., Simmons, A. D., Mohan, A.-M., Beindorff, N., Reineke, U., . . . Osterkamp, F. (2022). Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-022-05842-5
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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